Results

1. Description of sociodemographic and health status
characteristics of all patients evaluated for eligibility to participate in the
UNAIDS/MOH Drug Access Initiative.

1.1 - Socio demographic characteristics

1.1.1 Number of patients accessing the eligibility screening

As of March 31, 2000, 2144 patients presented to the accredited
centers for eligibility screening. The number of patients attending the
accredited centers for the first time since the beginning of the initiative is
summarized in Fig 1. This number includes patients who were already on ARV
therapy prior to the UNAIDS/MOH initiative but who joined the initiative because
of drug price reduction; 270 drug-experienced patients joined the Initiative of
whom 222 were taking ARV therapy at the time of this evaluation. An average of
113 new patients presented to the clinics each month. However, in December 1998,
a relatively small number of patients attended the clinics. In contrast, the
number of attendees exceeded 150 both in April and May 1999.

1.1.2 Clinics accessed and basic demographics

Men have been marginally in excess among those accessing the
initiative. Most have been Ivorian citizens residing in Abidjan (see table1).

Fig 1. Number of patients attending
the eligibility screening in the UNAIDS/MOH Drug Access Initiative in Cd'Ivoire, as of March 2000

Table 1. Number of patients (N=2144) by center and their
characteristics

Characteristics

N

Percent

Female

1038

(48)

Clinics

TB clinic Adjame

807

(37)

Infectious Diseases Department

585

(27)

USAC clinic

379

(18)

CIRBA clinic

183

(9)

Military Hospital

99

(5)

Pediatrics (Yopougon)

91

(4)

Ivoirian citizenship

1883

(87)

Residing in Abidjan

1638

(76)

1.1.3 Age

Overall distribution by age group is shown in Fig 2: the
majority of patients have been between 20 and 49 years old. Of those 20 years of
age or older, the mean age was 36 years (range 20-83). The percent of patients
under 20 years of age is approximately 5%: and among them, 20% were less than 5
years old. Of those under 20 years of age, the mean age was 7 (range 1
month-19).

Fig 2: Age group distribution among
patients accessing the UNAIDS/MOH Drug Access. Initiative in Cd'Ivoire,
August 1998-March 2000 (N=2144)

1.1.4 Economic and professional characteristics

There are a number of characteristics that may indirectly
indicate economic status of patients, such as the household daily food
expenditure. Approximately 55% of patients spend between 2 and 5 US dollars
daily for the food of the entire household.

The chart below represents the distribution of salary or monthly
income of patients presenting for eligibility screening. Of these patients, 40%
have no income and approximately 45% have an income between 50 and 400 US
dollars.

Approximately 35% of patients were the financial providers for
more than 4 adult persons and at least 3 children in their household.

Fig 4: Monthly income of patients
presenting for eligibility screening in the Initiative - Cd'Ivoire

A high percentage of patients had no professional activity.
Approximately 31% of patients accessing the Initiative have been manual
laborers, 26% salaried staff and 10% self employed (Fig 5).

Fig 5. Professional activity of
patients accessing the Initiative as of March 31,2000 - Cd'Ivoire

1.2. Health status

1.2.1 Medical characteristics

Table 2 below shows the HIV serostatus, CD4 counts, and clinical
status of patients accessing the UNAIDS/MOH Drug Access Initiative. Of all
patients attending the eligibility screening, 90% were infected with HIV-1, more
than 50% had a CD4 count of less than 200/µl, 55% met the 1993 CDC expanded
AIDS case definition, and 35% were taking chemoprophylaxis for opportunistic
infections, principally cotrimoxazole.

As shown in Table 3, few patients attending the eligibility
screening had abnormal biochemistry values using the ACTG (AIDS Clinical Trial
Group) classification scheme and a national evaluation scheme established by the
School of Pharmacy of University of Cd'Ivoire. Very few abnormal values
(grade 3 and 4) were recorded in the eligibility screening specimen of the three
different categories of patients. Among ARV-na patients, drug-experienced
patients receiving ARV, and drug-experienced patients not currently taking ARV,
the prevalence of severe anemia was 8%, 3% and 5% respectively. Regarding the
other biochemical parameters, fewer than 3% of patients in any group had
abnormal values.

Table 3. Percentage of abnormal values in eligibility screening
specimens of patients presenting for the Initiative

ACTG classification (grade 3 and/or 4)

ARV-na (n=1874)

Drug-experienced receiving ARV (n=222)

Drug-experienced not taking ARV (n=48)

Hemoglobin

8

3

5

Neutrophils

0

0

0

Platelets

1

1

0

Urea

0.5

0

2

Serum creatinine

1.5

0

3

SGOT

2

2

1

SGPT

0

0

0

Alkaline phosphatase

1

1

0

Amylase

0

0

0

Glycemia

0

0

0

1.2.2 Functional status

The major presenting symptoms were wasting, cough and fever.
Figure 6 below shows the functional status of patients at the time of
eligibility screening.

1.2.3 Clinical signs and symptomsUpon physical examination,
the most frequent clinical findings were the following:

Leucoplakia

208 (10%)

Cachexia

227 (10%)

Polyadenopathy

461 (21%)

Dermatitis

496 (23%)

Candidiasis

971 (45%)

2- Assessment of non-prescription and prescription of ARV
therapy

The second objective of this program evaluation is to identify
reasons why some patients who presented for the eligibility evaluation did not
receive ARV therapy. On Figure 7 is a flow chart with the status of na
patients with or without follow-up and prescription of therapy.

In this flow chart, 1874 na patients underwent the
eligibility screening. Of these, 794 (40%) did not return to the clinics to
obtain the results of the screening. An evaluation of the reasons for non-return
to the clinics is planned for later this year. Patients will be contacted either
by their care provider or social worker to document the reasons for non-return
to the clinics.

Of the 1874 ARV-na patients presenting for initial screening,
1080 (60%) returned to the clinics for further evaluation. Of these, 422
received ARV therapy and 658 did not. At the initial screening, an additional
270 ARV drug- experienced patients have also presented. Of them, 48 had a
history of ARV therapy but were not currently taking ARV drugs. These patients
are not represented in Figure 7.

The reasons for non-prescription of ARV therapy among na
patients who returned for further evaluation after initial screening have been
the following:

Decision for subsidy pending

255 (39%)

Abnormal serum chemistry

217 (33%)

Serum chemistry to be rechecked

136 (21%)

Data missing

96 (14.%)

Viral load <4 log10 copies and/or
CD4>500/µl

90 (14%)

The pending decision for subsidy accounts for the most important
reason of non-prescription. As of March 31, 2000, 255 patients were still
waiting to receive a decision on their application for subsidy. Of those, 86%
have been awaiting the decision for more than 2 months (Figure 8).

Subsidy in the UNAIDS/MOH Drug Access Initiative is allocated by
a National Committee and ranges from 50% to 95%. The table below compares
characteristics of patients paying full price for their ARV drugs and those who
obtained their drugs at a subsidized price.

Table 4. Characteristics of patients by subsidy category at
initiation of therapy in the Initiative (n=649)

Characteristics

Paid full price

50% subsidy

75% subsidy

95 % subsidy

Income <$200

72

75

80

83

CDC AIDS case definition

62

52

54

50

CD4 count < 200/µl (baseline)

71

73

57

62

Viral load > 10,000 copies/ml

52

72

70

69

Patients who paid the full price were marginally less likely to
have an income below US $200 compared with patients who received subsidies.

3. Follow-up of patients for whom ARVs are
prescribed

As of March 31, 2000, 649 patients have been prescribed therapy
through the UNAIDS Drug Access Initiative. Of these, 422 were ARV-na at the
time of initial screening.

Based on an average enrollment rate of 32 patients per month, it
is expected that 1152 patients would have started ARV therapy by August 2001.

Na and drug-experienced patients beginning therapy under the
initiative were compared regarding sociodemographic and clinical characteristics
(see Table 5). Na patients were more likely to have a monthly income of less
than US$ 200, lower CD4 counts at baseline, and were less likely to be on
prophylaxis for opportunistic infection than drug-experienced patients.

Table 5. Comparison among characteristics of na and
drug-experienced patients

Characteristics

Na (n=422)

Drug-experienced (n=222)

Mean age (years)

34

35

Female

41%

45%

Monthly income <US$ 200

68%

42%

Secondary education or lower

72%

69%

Median viral load at baseline (log10 copies/ml)

5.5

4.3

Median CD4 count at baseline (cells/µl)

89

192

Met CDC AIDS case definition

69%

33%

Taking OI prophylaxis

33%

45%

3.2 Evaluation of virological and immunological response to ARV
therapy.

Patients enrolled in the UNAIDS Drug Access Initiative have been
followed over time and evaluated biologically every 3 months. Patients have
undergone biochemistry evaluation, CD4 count and viral load testing. Response
for ARV-na patients will be the major focus in this chapter.

The assessment of virological and immunological response to ARV
therapy response will be presented in the following fashion:

Therapy information was categorized as 2NRTIs, HAART and other.
The analysis was conducted in two ways. Firstly, the response to therapy was
assessed in an as-treated analysis and then in an intent to treat analysis. The
latter is presented in the appendices 3 and 5. For both analyses, estimated
response to antiretroviral therapy at selected times (days) after initiation of
treatment was computed using the scatter plot smoother in S-PLUS software called
"super smoother". This method was used to be able to assess response to therapy
among patients who did not adhere to follow-up visits. This method uses
regression splines to fit a continuous curve to the data by piecing together
local fits to different portions of the data. The super smoother uses a
cross-validation method to choose the span of data used for each fit. Laboratory
measurements are assumed to be independent.

3.2.1. ARV-na patients3.2.1.1. As treated

This type of analysis is based on the effective time patients
have contributed to a specific type of therapy. Therefore, this analysis takes
into account any change from one type of therapy to another.

In general, patients accessing the UNAIDS/MOH Drug Access
Initiative were at an advanced stage of HIV infection upon accessing ARV
therapy. This analysis presents the occurrence of opportunistic infections over
time after initiating therapy. Figure 17 shows the time interval between
initiation of therapy to the time patients present with the first symptom of the
category B of the 1993 CDC expanded AIDS case definition. However, there are a
number of limitations to this approach since it was neither possible to
determine whether these patients had a previous history of AIDS nor to document
it. Therefore, patients with an AIDS indicator disease at initiation of therapy
were excluded and the clinical status used was based on the clinical examination
on the day of initiation of therapy. At 6 months, 11% of patients had
experienced at least one episode of opportunistic infection and this number
increased to 18% at 1 year. This analysis did not reveal any difference in the
different therapy groups. However, due to the limited number drug-experienced
patients it was not possible to conduct this analysis by history of ARV therapy.

Fig 17: Time from initiation of
therapy to the occurrence of the first opportunistic infection among patients
without O1 at initiation of therapy (n=254)

3.3.2 Tolerance of ARV

At the eligibility screening, patients had a serum sample drawn
for serum chemistry. The biochemistry evaluation is also performed on each
patient at each follow-up visit. This chapter refers to adverse events for
patients on ARV therapy. The severity grading is presented in the table below.
At initiation of therapy, very few patients had abnormal biochemistry results as
shown in the following table.

Table 6: Adverse events for patients on ARV therapy

Biochemistry

% with grade 3 or 4

Hemoglobin

4

Neutrophils

0

Platelets

1

Urea

0

Serum creatinine

0

SGOT

1

SGPT

0

Alkaline Phosphatase

1

Amylase

0

Glycemia

0

A Kaplan-Meier analysis was conducted to assess the time from
the initiation of ARV therapy to the occurrence of the first adverse event
(grade 3 or 4). Patients were censored at last visit or loss to follow up, and
the analysis was restricted to persons with follow-up, laboratory values (more
than 1 record per patient), excluding patients with adverse events at baseline.
Approximately 18% of patients had an adverse event within 12 months.

Fig 19: Time from initiation of
therapy to the occurrence of the first adverse event using ACTG classification
scheme (n=454)

3.3.3 AdherenceAdherence to therapy in the UNAIDS Drug
Access Initiative will be evaluated later this year.

3.3.4 Sustainability of therapyStatus of patients receiving
therapy was determined as of March 31, 2000 and patients were classified into
three major groups:

Patients active on ARV therapy: patients who had an
initial visit or a follow up visit in the 120 days prior to March 31, 2000, were
considered active on ARV therapy.

Patients known to have died: deaths are usually
reported by a family member or next-of kin

Patients considered lost to follow-up: if they did
not have any visit in the 120 days prior to March 31, 2000.

The results among the 649 patients who were receiving therapy
through the Drug Access Initiative are presented in the Figure 20 below.
Patients who are known to be alive and who stopped ARV therapy as of last visit
represent 2%. This number does not include patients who stopped and then resumed
ARV therapy.

The probability of a patient staying in care, who is active
taking ARV therapy was calculated by considering the patients who are known to
have stopped ARV therapy or those who are lost to follow-up. This probability is
74% at 6 months and 62% at 12 months. Patients who had died were considered to
have been actively on ARV therapy until their last visit and therefore were
censored in this analysis.

Fig 20: Status of patients enrolled
and receiving ARV therapy in the UNAIDS Drug Access Initiative as of March 31,
2000 -Cd'Ivoire

3.3.6 Causes of death

As of March 31, 2000, 44 patients were known to have died. There
has been no possibility to document the causes of death. The deaths were usually
reported by a family member or ascertained by a social worker when trying to
invite patients who are late for their follow-up visit to return to the clinic.
Therefore, there is possibility that the number of deaths reported may have been
underestimated.

3.4 Survival

Analysis of survival was conducted and results were divided into
two major components. The first analysis considers only patients known to have
died. The outcome event in this type of analysis was the death. All the other
categories of patients including those who stopped ARV therapy or were lost to
follow-up during this period were considered to be alive up to the last visit.

3.4.1 Overall survival

The overall survival has been 93% at 6 months, 90% at 12 months,
and 86% at 18 months. This effect is however not likely to reflect the reality
because deaths are passively reported to the care providers by the family
members.

Fig 21: Overall survival among
patients receiving therapy (n=649)

3.4.2 Survival and remaining in care

The next survival curve presents a worse case scenario where
patients who are lost to follow-up are considered to have died immediately after
their last visit. This situation is more likely to depict the reality and to
represent persons remaining in care in doctor's practice. In this curve,
survival is 75% at 6 months and 64% at 12 months. The 18-month survival is
approximately 55%.

Fig 22: Survival and remaining in care
-UNAIDS Drug Access Initiative

4. Laboratory cost

Projet RETRO-CI has provided logistic and laboratory technical
assistance in support of this initiative at its own expense during the 2-year
pilot phase of this evaluation. Results have routinely been forwarded to the
treating physician who decides whether to start ARV treatment. As set out in the
original protocol, RETRO-CI support of this initiative has been intended for the
purpose of evaluation and was not intended to be sustained beyond the period of
the evaluation.

At the outset of this Initiative, UNAIDS negotiated reduced
prices for certain ARVs through discussions with pharmaceutical companies. The
price reductions have come in the form of subsidies from a special solidarity
fund that was established by the Ivorian government and seeded with US$1
million. It has been hoped that this fund would be replenished by donations from
corporations, donor agencies, as well as special taxes. Eligibility for these
subsidies has been determined based on sociodemographic questionnaire data
obtained by a social worker and reviewed by a national committee. However,
another large part of the cost of sustaining ARV therapy is the costs of
providing laboratory support, and the majority of these costs are the kits or
diagnostic reagents themselves. As can be see in the Table below presenting the
costs to Projet RETRO-CI of the various tests that are used in evaluations and
in follow-up of each patient, the costs of reagents and diagnostic kits
represent the majority of the laboratory costs.

As set out in the Table 9 below, conservative calculations of
the total costs of the evaluations at RETRO-CI from August 1998 through March
2000 exceeded US$630,000. This represents a cost of almost $300 for every
patient presenting to the Initiative.

Whereas UNAIDS has negotiated reduced prices for certain ARVs
through discussions with pharmaceutical companies, similar negotiated price
reductions for the cost of diagnostic kits and reagents has not yet been
achieved. Based on the increasing numbers of patients being followed in this
Initiative, consideration should be given to seeking ways of lowering these
costs perhaps by working with the major marketers of diagnostic reagents and/or
seeking alternative sources of support for future laboratory needs of this
Initiative.

Summary

The results of this evaluation can be summarized in three
sections related to the initiative procedures and their attendant laboratory
costs:

Eligibility screening

· Over 20 months,
2144 patients have presented for the eligibility screening, with an average of
113 patients a month.· 23% of patients were
unemployed and 40% reported having no income.· 75% were symptomatic: the majority had a normal
activity· 15% had CD4 count above 500
cells/· Very few laboratory abnormal
baseline values are reported

Initiation of therapy

· 42% of patients
did not return for evaluation of their screening

· An average of 32 new patients
are prescribed ARV therapy a month

· The main reason for
non-prescription is the pending decision of the Committee regarding subsidy
approval.

· Among na patients, 53%
started therapy with a subsidy.

· At the time of enrollment in
the Initiative, ARV-na patients have tended to have a lower CD4 count, have a
higher baseline viral load, and have been more likely to meet the 1993 CDC
expended case definition

· Overall 2 NRTI has been the
most prescribed type of therapy, although recently HAART seems the preferred
choice of regimen.

Follow-up

· After 20 months of
therapy the status of follow-up is as follows: 2 % stopped, 7% died, 19% were
lost to follow-up and 71% were active on therapy.

· Viral dynamics indicate that
HAART has more promising results than 2NRTIs over time; however, so far there is
no effect on morbidity, mortality.

· Very few severe adverse events
in biochemistry values were reported.

Laboratory Costs

Projet RETRO-CI laboratory costs have been US
$631,646 or almost $1,000 for each of the 644 patients treated in the
Initiative. Most of these costs have been the costs of reagents and diagnostic
kits.